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31.
Verónica Corrales-Sánchez María del Mar Noblejas-López Cristina Nieto-Jiménez Javier Pérez-Peña Juan Carlos Montero Miguel Burgos Eva M. Galán-Moya Atanasio Pandiella Alberto Ocaña 《Journal of cellular and molecular medicine》2020,24(5):3117-3127
Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening. 相似文献
32.
Hector Moreno Alberto Rastrojo Rhys Pryce Chiara Fedeli Gert Zimmer Thomas A. Bowden Gisa Gerold Stefan Kunz 《PLoS neglected tropical diseases》2020,14(12)
A detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential. The recent isolation of Tacaribe and lymphocytic choriominingitis mammarenaviruses from host-seeking ticks provided evidence for the presence of mammarenaviruses in arthropods, which are established vectors for numerous other viral pathogens. Here, using next generation sequencing to search for other mammarenaviruses in ticks, we identified a novel replication-competent strain of the NW mammarenavirus Tamiami (TAMV-FL), which we found capable of utilizing hTfR1 to enter mammalian cells. During isolation through serial passaging in mammalian immunocompetent cells, the quasispecies of TAMV-FL acquired and enriched mutations leading to the amino acid changes N151K and D156N, within GP. Cell entry studies revealed that both substitutions, N151K and D156N, increased dependence of the virus on hTfR1 and binding to heparan sulfate proteoglycans. Moreover, we show that the substituted residues likely map to the sterically constrained trimeric axis of GP, and facilitate viral fusion at a lower pH, resulting in viral egress from later endosomal compartments. In summary, we identify and characterize a naturally occurring TAMV strain (TAMV-FL) within ticks that is able to utilize hTfR1. The TAMV-FL significantly diverged from previous TAMV isolates, demonstrating that TAMV quasispecies exhibit striking genetic plasticity that may facilitate zoonotic spillover and rapid adaptation to new hosts. 相似文献
33.
Delgado Naranjo Juan Martin Jiménez Callejón Maria José Peñuela Vásquez Mariana Rios Luis Alberto Robles Medina Alfonso 《Journal of applied phycology》2021,33(4):2031-2045
Journal of Applied Phycology - The thraustochytrid Aurantiochytrium limacinum SR21 is a promising source of docosahexaenoic acid (DHA) for human consumption as dietary supplement, replacing... 相似文献
34.
Manuele Gori Sara Maria Giannitelli Andrea Zancla Pamela Mozetic Marcella Trombetta Nicol Merendino Alberto Rainer 《Biotechnology and bioengineering》2021,118(1):142-152
Organs‐on‐chip (OoCs) are catching on as a promising and valuable alternative to animal models, in line with the 3Rs initiative. OoCs enable the creation of three‐dimensional (3D) tissue microenvironments with physiological and pathological relevance at unparalleled precision and complexity, offering new opportunities to model human diseases and to test the potential therapeutic effect of drugs, while overcoming the limited predictive accuracy of conventional 2D culture systems. Here, we present a liver‐on‐a‐chip model to investigate the effects of two naturally occurring polyphenols, namely quercetin and hydroxytyrosol, on nonalcoholic fatty liver disease (NAFLD) using a high‐content analysis readout methodology. NAFLD is currently the most common form of chronic liver disease; however, its complex pathogenesis is still far from being elucidated, and no definitive treatment has been established so far. In our experiments, we observed that both polyphenols seem to restrain the progression of the free fatty acid‐induced hepatocellular steatosis, showing a cytoprotective effect due to their antioxidant and lipid‐lowering properties. In conclusion, the findings of the present work could guide novel strategies to contrast the onset and progression of NAFLD. 相似文献
35.
Chromatin investigation in the nucleus using a phasor approach to structured illumination microscopy
Isotta Cainero Elena Cerutti Mario Faretta Gaetano Ivan Dellino Pier Giuseppe Pelicci Paolo Bianchini Giuseppe Vicidomini Alberto Diaspro Luca Lanzanò 《Biophysical journal》2021,120(12):2566-2576
Chromatin in the nucleus is organized in functional sites at variable level of compaction. Structured illumination microscopy (SIM) can be used to generate three-dimensional super-resolution (SR) imaging of chromatin by changing in phase and in orientation a periodic line illumination pattern. The spatial frequency domain is the natural choice to process SIM raw data and to reconstruct an SR image. Using an alternative approach, we demonstrate that the additional spatial information encoded in the knowledge of the position of the illumination pattern can be efficiently decoded using a generalized version of separation of photon by lifetime tuning (SPLIT) that does not require lifetime measurements. In the resulting SPLIT-SIM, the SR image is obtained by isolating a fraction of the intensity corresponding to the center of the diffraction-limited point spread function. This extends the use of the SPLIT approach from stimulated emission depletion microscopy to SIM. The SPLIT-SIM algorithm is based only on phasor analysis and does not require deconvolution. We show that SPLIT-SIM can be used to generate SR images of chromatin organizational motifs with tunable resolution and can be a valuable tool for the imaging of functional sites in the nucleus. 相似文献
36.
37.
Alberto Cornejo Julio Caballero Mario Simirgiotis Vanessa Torres Luisa Snchez Nicols Díaz Marcela Guimaraes Marcos Hernndez Carlos Areche Sergio Alfaro Leonardo Caballero Francisco Melo 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):154
Parkinson''s disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1. Also, aggregates treated with 1 do not provoke neurites'' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44. 相似文献
38.
Alonso Alberto Pérez Javier Monroy Silvia López-Rojo Naiara Basaguren Ana Bosch Jaime Boyero Luz 《Ecosystems》2021,24(6):1436-1449
Ecosystems - Leaf litter of alder (Alnus glutinosa) is a key resource to detrital stream food webs. Due to its high quality and palatability, it is readily colonised by microorganisms and consumed... 相似文献
39.
Yesenia Pacheco-Hernández Carlos Jonnathan Castro-Juárez Sergio Alberto Ramírez-García Ramiro Cruz-Durán Edmundo Lozoya-Gloria Nemesio Villa-Ruano 《Journal of Asia》2021,24(2):243-249
Preventive measures based in the control of insect vectors are considered as the best choice to decrease the incidence of insect-borne diseases. Herein we report on the volatile content of the leaf essential oils from Marina neglecta, a medicinal plant distributed in the tropical regions of southern Mexico. In order to investigate the chemical variation of the essential oils, a volatile screening was performed during the four seasons of the years 2016–2019. Simultaneously, their biological activity was tested on distinct life stages of Meccus pallidipennis, M. bassolsae, Aedes aegypti and A. albopictus. Essential oils were mainly constituted of β-pinene (>30%) β-caryophyllene (>25%) and germacrene D (>13%). Dorsal-abdomen application of essential oils on triatomines, revealed an efficient LC50 for nymphs of the stages I to III (4 µg/insect), nymphs of the stages IV to V (5–6 µg/insect), and adults (7–8 µg/insect). The LT50 for the stages I to III was between 6 and 8 h, whereas that for the stages IV to V and adults oscillated between 12 and 16 h and 22 to 26 h, respectively. Fumigation experiments performed on nymph V, demonstrated that 300 µg L?1 air produced 100% mortality after 72 h post-treatment. Among tested volatiles, β-pinene and β-caryophyllene produced a comparable mortality rate (p < 0.01) than that of essential oils in the stages assayed. Essential oils showed strong larvicidal (LC50, 24–36 µg mL?1) and adulticidal (35–48 µg mL?1) activities in mosquito species with an LT50 of 4.5 h and 25–35 min, respectively. The evaluation of β-pinene produced a significant mortality rate (p < 0.01) in larvae whereas germacrene D was the most effective volatile (p < 0.01) against adults of both mosquito species. According to our results, β-pinene was the most effective volatile against the four insect species evaluated and its effect was comparable to that of the essential oil. 相似文献
40.
Jana Krajňáková Alberto Bertolini Dušan Gömöry Angelo Vianello Hely Häggman 《In vitro cellular & developmental biology. Plant》2013,49(5):560-571
Somatic embryogenesis of Abies alba (Mill.) has significant potential to become an effective method for vegetative propagation of this species. To induce somatic embryogenesis in A. alba, the influence of the mother tree, sampling dates, and cold treatment storage of cones were examined. The initiation frequencies ranged from 1.7% to 16.6%. The sampling date and cone storage, but not the mother tree, had a significant effect on the initiation of embryogenic cultures. Storage of embryogenic cell lines was tested through cryopreservation for 6 yr. Four out of 12 cryostored embryogenic cell lines recovered, and the regeneration of cotyledonary embryos was obtained with two cell lines. The ability of embryogenic cell masses to produce somatic embryos and the mean number of cotyledonary embryos were higher when the maturation protocol was based on embryogenic suspensions dispersed on filter paper. The properly developed germinants were obtained only from maturation media where 32 μM abscisic acid was used, being 16.2% when polyethylene glycol (PEG) was not present and 1.8% when supplemented with 10% (w/v) PEG, respectively. The present study provides evidence that it is possible to cryopreserve A. alba embryogenic cultures while maintaining their maturing ability for the lengthy period (6 yr) needed for progeny testing of field-grown trees. Therefore, our findings are important for further studies and advanced breeding work of the species; however, the conversion of germinants into ex vitro conditions still remains a significant challenge. 相似文献